CHOPPI: a web tool for the analysis of immunogenicity risk from host cell proteins in CHO-based protein production.
CHOPPI: a web tool for the analysis of immunogenicity risk from host cell proteins in CHO-based protein production.
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DOI：
10.1002/bit.25286
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发表时间：
2014-11
影响因子：
3.8
通讯作者：
De Groot, Anne S.
中科院分区：
文献类型：
--
作者：
Bailey-Kellogg, Chris;Gutierrez, Andres H.;Moise, Leonard;Terry, Frances;Martin, William D.;De Groot, Anne S.
尽管制造过程中具有很高的质量标准和不断的工艺改进，但宿主细胞蛋白 (HCP) 工艺杂质仍然是生物制品的重大风险。即使水平较低，残留的 HCP 也会诱发有害的免疫反应，从而损害生物制剂的安全性和有效性。因此，由于发现了针对 HCP 的抗体，晚期临床试验已被取消。为了更早、快速地评估基于中国仓鼠卵巢 (CHO) 的蛋白质生产中残留 CHO 蛋白质杂质 (CHOP) 的风险，我们开发了一种名为 CHOPPI 的网络工具，用于 CHO 蛋白质预测免疫原性。 CHOPPI 整合了有关 CHOP 可能存在（表达和分泌）的信息及其免疫原性特征（T 细胞表位计数和密度，以及与人类对应物的相对保守性）。 CHOPPI 可以生成特定 CHO 蛋白的报告（例如，从蛋白质组学或免疫测定中鉴定）或表征 CHO 基因组的整个特定子集（例如，根据转录置信度和与人类蛋白质的相似性进行过滤）。在基因组规模上分析潜在 CHOP 的能力为评估相对风险提供了基线。我们在此表明，CHOPPI 可以识别先前验证的 CHOP 之间免疫原性风险的明显差异，以及识别可能在生产过程中表达并在交付时诱导有害免疫反应的其他“风险”CHO 蛋白。我们的结论是，CHOPPI 是一个强大的工具，它为 CHOP 风险评估的现有实验方法提供了有价值的计算补充，并且可以将实验工作集中在最重要的方向上。生物技术。生物工程。 2014；111：2170–2182。
Despite high quality standards and continual process improvements in manufacturing, host cell protein (HCP) process impurities remain a substantial risk for biological products. Even at low levels, residual HCPs can induce a detrimental immune response compromising the safety and efficacy of a biologic. Consequently, advanced-stage clinical trials have been cancelled due to the identification of antibodies against HCPs. To enable earlier and rapid assessment of the risks in Chinese Hamster Ovary (CHO)-based protein production of residual CHO protein impurities (CHOPs), we have developed a web tool called CHOPPI, for CHO Protein Predicted Immunogenicity. CHOPPI integrates information regarding the possible presence of CHOPs (expression and secretion) with characterizations of their immunogenicity (T cell epitope count and density, and relative conservation with human counterparts). CHOPPI can generate a report for a specified CHO protein (e.g., identified from proteomics or immunoassays) or characterize an entire specified subset of the CHO genome (e.g., filtered based on confidence in transcription and similarity to human proteins). The ability to analyze potential CHOPs at a genomic scale provides a baseline to evaluate relative risk. We show here that CHOPPI can identify clear differences in immunogenicity risk among previously validated CHOPs, as well as identify additional “risky” CHO proteins that may be expressed during production and induce a detrimental immune response upon delivery. We conclude that CHOPPI is a powerful tool that provides a valuable computational complement to existing experimental approaches for CHOP risk assessment and can focus experimental efforts in the most important directions. Biotechnol. Bioeng. 2014;111: 2170–2182.
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影响因子：
4.8
作者：
Gutiérrez AH;Moise L;De Groot AS
通讯作者：
De Groot AS
影响因子：
4.8
作者：
De Groot, AS;Bishop, EA;Martin, W
通讯作者：
Martin, W
影响因子：
4.1
作者：
Becker, Jennifer;Hackl, Matthias;Brinkrolf, Karina
通讯作者：
Brinkrolf, Karina
影响因子：
5.3
作者：
Doneanu, Catalin E.;Xenopoulos, Alex;Chen, Weibin
通讯作者：
Chen, Weibin
影响因子：
3
作者：
Higgins, Elizabeth
通讯作者：
Higgins, Elizabeth